Compartmentalized Postoperative Radiotherapy in Head and Neck Cancer

Inclusion criteria 1. ECOG performance status 0-2 at the time of registration 2. ≥18 years of age 3. Baseline assessments and documentation of toxicity using CTCAE v.5 and QoL using MDADI, EORTC C30 and HN43 questionnaires. 4. Histopathologically confirmed, surgically treated squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx 5. Previous neoadjuvant systemic therapy (chemotherapy, immunotherapy or combinations, e.g. KEYNOTE-68922) is permitted only if its neoadjuvant use for locally advanced HNSCC is approved by Swissmedic and routinely reimbursed at the time it was administered or if it was administered as part of routine institutional treatment decisions, outside of a clinical trial or other investigational framework. 6. Standard indication for PORT via external beam radiotherapy (with or without concomitant systemic treatment) defined by a multidisciplinary head and neck tumor board (MDT). 7. History and physical examination by treating radiation oncologist within 28 days prior to registration. 8. MRI of the head and neck (or computerized tomography as substitute) with i.v. contrast, if not contraindicated. CT of the chest with i.v. contrast, if not contraindicated. 18FDG-PET/CT can be used instead of CT of the chest. The baseline imaging examinations include the preoperative diagnostic phase and do not have to be repeated if performed within 60 days prior to the enrollment. 9. The multidisciplinary team (MDT) must determine that the patient can safely undergo the standard treatment, which may include PORT with or without additional systemic treatment. 10. Post-menopausal women, or women of child-bearing potential who use or agree to use effective contraception, are not pregnant and agree not to become pregnant during and within 30 days after PORT. A negative pregnancy test before inclusion (within 28 days) into the trial is required for all women with child-bearing potential. Men agree not to father a child during and within three months after PORT. 11. Written informed consent, signed by the patient and the investigator. Exclusion criteria 1. Synchronous or previous malignancies. Exceptions are curatively treated basal cell carcinoma or SCC of the skin, or in situ carcinoma of the cervix uteri, low- or intermediate- risk prostate cancer, or breast with a progression-free follow-up time of at least 3 years without any remaining disease burden, or other previous malignancy with a progression-free interval of at least 5 years without any remaining active/progressive disease burden regardless whether the treatment is completed or ongoing as a maintenance treatment (e.g. androgen deprivation therapy for prostate cancer). 2. Presence of distant metastases c/pM1. 3. Recurrent HNSCC 4. Neoadjuvant systemic therapy administered under a clinical trial protocol or as part of any structured investigational framework not considered standard institutional practice at the time of administration. 5. Previous neck dissection prior to the diagnosis of the index tumor 6. Previous radiation dose applied to the anatomical sites overlapping with the standard PORT target volumes which may have a potential impact on the delivered dose and/or toxicity profile of the standard PORT. 7. R2 resection of the primary tumor or macroscopic residual disease of any involved lymph node. 8. Last oncologic surgery for the index HNSCC performed more than 6 weeks ago. 9. Inadequate reporting of the pathology not conformal with COMPORT algorithm and no possibility of an adequate post-hoc acquisition of the necessary information (see the section 8) 10. Co-existing disease prejudicing survival (expected survival less than 6 months). 11. Active bacterial or fungal infection requiring intravenous antibiotics at the time of registration. 12. Illness expected to preclude PORT within 7 days of registration. 13. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. 14. Ongoing participation in another interventional clinical trial which are not exempted by the sponsor. Exceptions may apply depending on the trial methodology (Please contact sponsor for clarification).